Translatomic response of retinal Müller glia to acute and chronic stress

Analysis of retina cell type-specific epigenetic and transcriptomic signatures is crucial to understanding the pathophysiology of retinal degenerations such as age-related macular degeneration (AMD) and delineating cell autonomous and cell-non-autonomous mechanisms. We have discovered that Aldh1l1 i...
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Autor*in:	Ana J. Chucair-Elliott [verfasserIn] Sarah R. Ocañas [verfasserIn] Kevin Pham [verfasserIn] Michael Van Der Veldt [verfasserIn] Ashley Cheyney [verfasserIn] David Stanford [verfasserIn] Jami Gurley [verfasserIn] Michael H. Elliott [verfasserIn] Willard M. Freeman [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Müller glia Retina Transcriptome Epigenome Acute stress Optic nerve crush

Übergeordnetes Werk:	In: Neurobiology of Disease - Elsevier, 2021, 175(2022), Seite 105931-
Übergeordnetes Werk:	volume:175 ; year:2022 ; pages:105931-

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.nbd.2022.105931

Katalog-ID:	DOAJ083380434

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allfields	10.1016/j.nbd.2022.105931 doi (DE-627)DOAJ083380434 (DE-599)DOAJd743193742944ce09be1911b654c85e5 DE-627 ger DE-627 rakwb eng RC321-571 Ana J. Chucair-Elliott verfasserin aut Translatomic response of retinal Müller glia to acute and chronic stress 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Analysis of retina cell type-specific epigenetic and transcriptomic signatures is crucial to understanding the pathophysiology of retinal degenerations such as age-related macular degeneration (AMD) and delineating cell autonomous and cell-non-autonomous mechanisms. We have discovered that Aldh1l1 is specifically expressed in the major macroglia of the retina, Müller glia, and, unlike the brain, is not expressed in retinal astrocytes. This allows use of Aldh1l1 cre drivers and Nuclear Tagging and Translating Ribosome Affinity Purification (NuTRAP) constructs for temporally controlled labeling and paired analysis of Müller glia epigenomes and translatomes. As validated through a variety of approaches, the Aldh1l1cre/ERT2-NuTRAP model provides Müller glia specific translatomic and epigenomic profiles without the need to isolate whole cells. Application of this approach to models of acute injury (optic nerve crush) and chronic stress (aging) uncovered few common Müller glia-specific transcriptome changes in inflammatory pathways, and mostly differential signatures for each stimulus. The expression of members of the IL-6 and integrin-linked kinase signaling pathways was enhanced in Müller glia in response to optic nerve crush but not aging. Unique changes in neuroinflammation and fibrosis signaling pathways were observed in response to aging but not with optic nerve crush. The Aldh1l1cre/ERT2-NuTRAP model allows focused molecular analyses of a single, minority cell type within the retina, providing more substantial effect sizes than whole tissue analyses. The NuTRAP model, nucleic acid isolation, and validation approaches presented here can be applied to any retina cell type for which a cell type-specific cre is available. Müller glia Retina Transcriptome Epigenome Acute stress Optic nerve crush Neurosciences. Biological psychiatry. Neuropsychiatry Sarah R. Ocañas verfasserin aut Kevin Pham verfasserin aut Michael Van Der Veldt verfasserin aut Ashley Cheyney verfasserin aut David Stanford verfasserin aut Jami Gurley verfasserin aut Michael H. Elliott verfasserin aut Willard M. Freeman verfasserin aut In Neurobiology of Disease Elsevier, 2021 175(2022), Seite 105931- (DE-627)268125414 (DE-600)1471408-5 1095953X nnns volume:175 year:2022 pages:105931- https://doi.org/10.1016/j.nbd.2022.105931 kostenfrei https://doaj.org/article/d743193742944ce09be1911b654c85e5 kostenfrei http://www.sciencedirect.com/science/article/pii/S0969996122003230 kostenfrei https://doaj.org/toc/1095-953X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 175 2022 105931-
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allfields_unstemmed	10.1016/j.nbd.2022.105931 doi (DE-627)DOAJ083380434 (DE-599)DOAJd743193742944ce09be1911b654c85e5 DE-627 ger DE-627 rakwb eng RC321-571 Ana J. Chucair-Elliott verfasserin aut Translatomic response of retinal Müller glia to acute and chronic stress 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Analysis of retina cell type-specific epigenetic and transcriptomic signatures is crucial to understanding the pathophysiology of retinal degenerations such as age-related macular degeneration (AMD) and delineating cell autonomous and cell-non-autonomous mechanisms. We have discovered that Aldh1l1 is specifically expressed in the major macroglia of the retina, Müller glia, and, unlike the brain, is not expressed in retinal astrocytes. This allows use of Aldh1l1 cre drivers and Nuclear Tagging and Translating Ribosome Affinity Purification (NuTRAP) constructs for temporally controlled labeling and paired analysis of Müller glia epigenomes and translatomes. As validated through a variety of approaches, the Aldh1l1cre/ERT2-NuTRAP model provides Müller glia specific translatomic and epigenomic profiles without the need to isolate whole cells. Application of this approach to models of acute injury (optic nerve crush) and chronic stress (aging) uncovered few common Müller glia-specific transcriptome changes in inflammatory pathways, and mostly differential signatures for each stimulus. The expression of members of the IL-6 and integrin-linked kinase signaling pathways was enhanced in Müller glia in response to optic nerve crush but not aging. Unique changes in neuroinflammation and fibrosis signaling pathways were observed in response to aging but not with optic nerve crush. The Aldh1l1cre/ERT2-NuTRAP model allows focused molecular analyses of a single, minority cell type within the retina, providing more substantial effect sizes than whole tissue analyses. The NuTRAP model, nucleic acid isolation, and validation approaches presented here can be applied to any retina cell type for which a cell type-specific cre is available. Müller glia Retina Transcriptome Epigenome Acute stress Optic nerve crush Neurosciences. Biological psychiatry. Neuropsychiatry Sarah R. Ocañas verfasserin aut Kevin Pham verfasserin aut Michael Van Der Veldt verfasserin aut Ashley Cheyney verfasserin aut David Stanford verfasserin aut Jami Gurley verfasserin aut Michael H. Elliott verfasserin aut Willard M. Freeman verfasserin aut In Neurobiology of Disease Elsevier, 2021 175(2022), Seite 105931- (DE-627)268125414 (DE-600)1471408-5 1095953X nnns volume:175 year:2022 pages:105931- https://doi.org/10.1016/j.nbd.2022.105931 kostenfrei https://doaj.org/article/d743193742944ce09be1911b654c85e5 kostenfrei http://www.sciencedirect.com/science/article/pii/S0969996122003230 kostenfrei https://doaj.org/toc/1095-953X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 175 2022 105931-
allfieldsGer	10.1016/j.nbd.2022.105931 doi (DE-627)DOAJ083380434 (DE-599)DOAJd743193742944ce09be1911b654c85e5 DE-627 ger DE-627 rakwb eng RC321-571 Ana J. Chucair-Elliott verfasserin aut Translatomic response of retinal Müller glia to acute and chronic stress 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Analysis of retina cell type-specific epigenetic and transcriptomic signatures is crucial to understanding the pathophysiology of retinal degenerations such as age-related macular degeneration (AMD) and delineating cell autonomous and cell-non-autonomous mechanisms. We have discovered that Aldh1l1 is specifically expressed in the major macroglia of the retina, Müller glia, and, unlike the brain, is not expressed in retinal astrocytes. This allows use of Aldh1l1 cre drivers and Nuclear Tagging and Translating Ribosome Affinity Purification (NuTRAP) constructs for temporally controlled labeling and paired analysis of Müller glia epigenomes and translatomes. As validated through a variety of approaches, the Aldh1l1cre/ERT2-NuTRAP model provides Müller glia specific translatomic and epigenomic profiles without the need to isolate whole cells. Application of this approach to models of acute injury (optic nerve crush) and chronic stress (aging) uncovered few common Müller glia-specific transcriptome changes in inflammatory pathways, and mostly differential signatures for each stimulus. The expression of members of the IL-6 and integrin-linked kinase signaling pathways was enhanced in Müller glia in response to optic nerve crush but not aging. Unique changes in neuroinflammation and fibrosis signaling pathways were observed in response to aging but not with optic nerve crush. The Aldh1l1cre/ERT2-NuTRAP model allows focused molecular analyses of a single, minority cell type within the retina, providing more substantial effect sizes than whole tissue analyses. The NuTRAP model, nucleic acid isolation, and validation approaches presented here can be applied to any retina cell type for which a cell type-specific cre is available. Müller glia Retina Transcriptome Epigenome Acute stress Optic nerve crush Neurosciences. Biological psychiatry. Neuropsychiatry Sarah R. Ocañas verfasserin aut Kevin Pham verfasserin aut Michael Van Der Veldt verfasserin aut Ashley Cheyney verfasserin aut David Stanford verfasserin aut Jami Gurley verfasserin aut Michael H. Elliott verfasserin aut Willard M. Freeman verfasserin aut In Neurobiology of Disease Elsevier, 2021 175(2022), Seite 105931- (DE-627)268125414 (DE-600)1471408-5 1095953X nnns volume:175 year:2022 pages:105931- https://doi.org/10.1016/j.nbd.2022.105931 kostenfrei https://doaj.org/article/d743193742944ce09be1911b654c85e5 kostenfrei http://www.sciencedirect.com/science/article/pii/S0969996122003230 kostenfrei https://doaj.org/toc/1095-953X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 175 2022 105931-
allfieldsSound	10.1016/j.nbd.2022.105931 doi (DE-627)DOAJ083380434 (DE-599)DOAJd743193742944ce09be1911b654c85e5 DE-627 ger DE-627 rakwb eng RC321-571 Ana J. Chucair-Elliott verfasserin aut Translatomic response of retinal Müller glia to acute and chronic stress 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Analysis of retina cell type-specific epigenetic and transcriptomic signatures is crucial to understanding the pathophysiology of retinal degenerations such as age-related macular degeneration (AMD) and delineating cell autonomous and cell-non-autonomous mechanisms. We have discovered that Aldh1l1 is specifically expressed in the major macroglia of the retina, Müller glia, and, unlike the brain, is not expressed in retinal astrocytes. This allows use of Aldh1l1 cre drivers and Nuclear Tagging and Translating Ribosome Affinity Purification (NuTRAP) constructs for temporally controlled labeling and paired analysis of Müller glia epigenomes and translatomes. As validated through a variety of approaches, the Aldh1l1cre/ERT2-NuTRAP model provides Müller glia specific translatomic and epigenomic profiles without the need to isolate whole cells. Application of this approach to models of acute injury (optic nerve crush) and chronic stress (aging) uncovered few common Müller glia-specific transcriptome changes in inflammatory pathways, and mostly differential signatures for each stimulus. The expression of members of the IL-6 and integrin-linked kinase signaling pathways was enhanced in Müller glia in response to optic nerve crush but not aging. Unique changes in neuroinflammation and fibrosis signaling pathways were observed in response to aging but not with optic nerve crush. The Aldh1l1cre/ERT2-NuTRAP model allows focused molecular analyses of a single, minority cell type within the retina, providing more substantial effect sizes than whole tissue analyses. The NuTRAP model, nucleic acid isolation, and validation approaches presented here can be applied to any retina cell type for which a cell type-specific cre is available. Müller glia Retina Transcriptome Epigenome Acute stress Optic nerve crush Neurosciences. Biological psychiatry. Neuropsychiatry Sarah R. Ocañas verfasserin aut Kevin Pham verfasserin aut Michael Van Der Veldt verfasserin aut Ashley Cheyney verfasserin aut David Stanford verfasserin aut Jami Gurley verfasserin aut Michael H. Elliott verfasserin aut Willard M. Freeman verfasserin aut In Neurobiology of Disease Elsevier, 2021 175(2022), Seite 105931- (DE-627)268125414 (DE-600)1471408-5 1095953X nnns volume:175 year:2022 pages:105931- https://doi.org/10.1016/j.nbd.2022.105931 kostenfrei https://doaj.org/article/d743193742944ce09be1911b654c85e5 kostenfrei http://www.sciencedirect.com/science/article/pii/S0969996122003230 kostenfrei https://doaj.org/toc/1095-953X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 175 2022 105931-
language	English
source	In Neurobiology of Disease 175(2022), Seite 105931- volume:175 year:2022 pages:105931-
sourceStr	In Neurobiology of Disease 175(2022), Seite 105931- volume:175 year:2022 pages:105931-
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Müller glia Retina Transcriptome Epigenome Acute stress Optic nerve crush Neurosciences. Biological psychiatry. Neuropsychiatry
isfreeaccess_bool	true
container_title	Neurobiology of Disease
authorswithroles_txt_mv	Ana J. Chucair-Elliott @@aut@@ Sarah R. Ocañas @@aut@@ Kevin Pham @@aut@@ Michael Van Der Veldt @@aut@@ Ashley Cheyney @@aut@@ David Stanford @@aut@@ Jami Gurley @@aut@@ Michael H. Elliott @@aut@@ Willard M. Freeman @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	268125414
id	DOAJ083380434
language_de	englisch
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callnumber-first	R - Medicine
author	Ana J. Chucair-Elliott
spellingShingle	Ana J. Chucair-Elliott misc RC321-571 misc Müller glia misc Retina misc Transcriptome misc Epigenome misc Acute stress misc Optic nerve crush misc Neurosciences. Biological psychiatry. Neuropsychiatry Translatomic response of retinal Müller glia to acute and chronic stress
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topic_title	RC321-571 Translatomic response of retinal Müller glia to acute and chronic stress Müller glia Retina Transcriptome Epigenome Acute stress Optic nerve crush
topic	misc RC321-571 misc Müller glia misc Retina misc Transcriptome misc Epigenome misc Acute stress misc Optic nerve crush misc Neurosciences. Biological psychiatry. Neuropsychiatry
topic_unstemmed	misc RC321-571 misc Müller glia misc Retina misc Transcriptome misc Epigenome misc Acute stress misc Optic nerve crush misc Neurosciences. Biological psychiatry. Neuropsychiatry
topic_browse	misc RC321-571 misc Müller glia misc Retina misc Transcriptome misc Epigenome misc Acute stress misc Optic nerve crush misc Neurosciences. Biological psychiatry. Neuropsychiatry
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title	Translatomic response of retinal Müller glia to acute and chronic stress
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title_full	Translatomic response of retinal Müller glia to acute and chronic stress
author_sort	Ana J. Chucair-Elliott
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author_browse	Ana J. Chucair-Elliott Sarah R. Ocañas Kevin Pham Michael Van Der Veldt Ashley Cheyney David Stanford Jami Gurley Michael H. Elliott Willard M. Freeman
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author-letter	Ana J. Chucair-Elliott
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title_sort	translatomic response of retinal müller glia to acute and chronic stress
callnumber	RC321-571
title_auth	Translatomic response of retinal Müller glia to acute and chronic stress
abstract	Analysis of retina cell type-specific epigenetic and transcriptomic signatures is crucial to understanding the pathophysiology of retinal degenerations such as age-related macular degeneration (AMD) and delineating cell autonomous and cell-non-autonomous mechanisms. We have discovered that Aldh1l1 is specifically expressed in the major macroglia of the retina, Müller glia, and, unlike the brain, is not expressed in retinal astrocytes. This allows use of Aldh1l1 cre drivers and Nuclear Tagging and Translating Ribosome Affinity Purification (NuTRAP) constructs for temporally controlled labeling and paired analysis of Müller glia epigenomes and translatomes. As validated through a variety of approaches, the Aldh1l1cre/ERT2-NuTRAP model provides Müller glia specific translatomic and epigenomic profiles without the need to isolate whole cells. Application of this approach to models of acute injury (optic nerve crush) and chronic stress (aging) uncovered few common Müller glia-specific transcriptome changes in inflammatory pathways, and mostly differential signatures for each stimulus. The expression of members of the IL-6 and integrin-linked kinase signaling pathways was enhanced in Müller glia in response to optic nerve crush but not aging. Unique changes in neuroinflammation and fibrosis signaling pathways were observed in response to aging but not with optic nerve crush. The Aldh1l1cre/ERT2-NuTRAP model allows focused molecular analyses of a single, minority cell type within the retina, providing more substantial effect sizes than whole tissue analyses. The NuTRAP model, nucleic acid isolation, and validation approaches presented here can be applied to any retina cell type for which a cell type-specific cre is available.
abstractGer	Analysis of retina cell type-specific epigenetic and transcriptomic signatures is crucial to understanding the pathophysiology of retinal degenerations such as age-related macular degeneration (AMD) and delineating cell autonomous and cell-non-autonomous mechanisms. We have discovered that Aldh1l1 is specifically expressed in the major macroglia of the retina, Müller glia, and, unlike the brain, is not expressed in retinal astrocytes. This allows use of Aldh1l1 cre drivers and Nuclear Tagging and Translating Ribosome Affinity Purification (NuTRAP) constructs for temporally controlled labeling and paired analysis of Müller glia epigenomes and translatomes. As validated through a variety of approaches, the Aldh1l1cre/ERT2-NuTRAP model provides Müller glia specific translatomic and epigenomic profiles without the need to isolate whole cells. Application of this approach to models of acute injury (optic nerve crush) and chronic stress (aging) uncovered few common Müller glia-specific transcriptome changes in inflammatory pathways, and mostly differential signatures for each stimulus. The expression of members of the IL-6 and integrin-linked kinase signaling pathways was enhanced in Müller glia in response to optic nerve crush but not aging. Unique changes in neuroinflammation and fibrosis signaling pathways were observed in response to aging but not with optic nerve crush. The Aldh1l1cre/ERT2-NuTRAP model allows focused molecular analyses of a single, minority cell type within the retina, providing more substantial effect sizes than whole tissue analyses. The NuTRAP model, nucleic acid isolation, and validation approaches presented here can be applied to any retina cell type for which a cell type-specific cre is available.
abstract_unstemmed	Analysis of retina cell type-specific epigenetic and transcriptomic signatures is crucial to understanding the pathophysiology of retinal degenerations such as age-related macular degeneration (AMD) and delineating cell autonomous and cell-non-autonomous mechanisms. We have discovered that Aldh1l1 is specifically expressed in the major macroglia of the retina, Müller glia, and, unlike the brain, is not expressed in retinal astrocytes. This allows use of Aldh1l1 cre drivers and Nuclear Tagging and Translating Ribosome Affinity Purification (NuTRAP) constructs for temporally controlled labeling and paired analysis of Müller glia epigenomes and translatomes. As validated through a variety of approaches, the Aldh1l1cre/ERT2-NuTRAP model provides Müller glia specific translatomic and epigenomic profiles without the need to isolate whole cells. Application of this approach to models of acute injury (optic nerve crush) and chronic stress (aging) uncovered few common Müller glia-specific transcriptome changes in inflammatory pathways, and mostly differential signatures for each stimulus. The expression of members of the IL-6 and integrin-linked kinase signaling pathways was enhanced in Müller glia in response to optic nerve crush but not aging. Unique changes in neuroinflammation and fibrosis signaling pathways were observed in response to aging but not with optic nerve crush. The Aldh1l1cre/ERT2-NuTRAP model allows focused molecular analyses of a single, minority cell type within the retina, providing more substantial effect sizes than whole tissue analyses. The NuTRAP model, nucleic acid isolation, and validation approaches presented here can be applied to any retina cell type for which a cell type-specific cre is available.
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title_short	Translatomic response of retinal Müller glia to acute and chronic stress
url	https://doi.org/10.1016/j.nbd.2022.105931 https://doaj.org/article/d743193742944ce09be1911b654c85e5 http://www.sciencedirect.com/science/article/pii/S0969996122003230 https://doaj.org/toc/1095-953X
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